Process of making theophyllin.



, UNITED STATES Patented August 23, 1904.

PATENT OFFICE.-

MITFORD C. MASSIE, OF WASHINGTON, DISTRICT OF COLUMBIA, ADMIN ISTRATOR OF FRITZ ACH, DECEASED, ASSIGNOR TO C. F. BOEHRINGER.

& SOEHNE, OF MANNHEIM-WALDHOF, GERMANY, A FIRM.

PROCESS OFYMAKING THEOPHYLLIN.

SPECIFICATION forming part of Letters Patent No. 768,533, dated August 23, 1904.

Original application filed February '7, 1903, Serial Np. 142,591. Divided and this application filed January 25, 190 Serial Ila-190.566. (Nospecimens) To all whom, it may concern:

Be it known that FRITZ AoH, deceased, late a citizen of Germany, and a resident of Mannheim, Germany, did invent new and useful Im- 5 provements in the Preparation of Theophyllin;

and I, MITFOBD C. MASSIE, residing at Washington, District of Columbia, the duly-constituted administrator of the estate of said FRITZ ACH, deceased, do hereby declare the follow- 1 ing to be a full, clear, and exact description of the said invention of said decedent, such as will enable others skilled in the art to which it appertains to make and use the same, the said invention being described but not specif- I icallyclaimed in application Serial No. 142, 591,

filed February 7, 1903, of which this is a divisional application.

In United States Patent No. 660,7 1 1 a process for the preparation of paraxanthin or 1.7- dimethylxanthin has been described. That process starts with a 1.7 -dimethyl-3-chloro methyl-S-chloroxanthin, having the structural formula 2 emu-co 5 l l I O0 CN .CHs C.Cl CH2. C1.NCN

3 and which, as set forth in said patent, is prepared by subjecting 8-chlorocaffein to the chlorinizing action of a mixture of phosphorus pentachlorid and phosphorus oxychlorid at a temperature of about 150 centigrade.

tuted xanthin employed under the aforesaid patent; but the chlorin atom takes the place of hydrogen atom in the methyl group in the position 7, so that in this case a7 -8dichloro caffein, having the structural formula is obtained. In this 7 -8-dichlorocaffein the chloromethyl group is readily split ofl similarly to the isomers described in the said United States Patent No.- 660/74 1 If this body is heated with water, dilute acids, or alkalies, it is hydrolized concurrently with the formation of formic aldehyde and hydrochloric acid, 8-chlorotheophyllin or 1.3-dimethyl-S-chloroxanthin being formed accord-. ing to the equation (7-8-dich1orocaifein) CH3.NOO

.H OC CN CH2.O+HCl l u oo1 CH3.NCN

(8ch1orotheophyl1in) The chlorotheophyllin thus obtained may readily be converted into the valuable therapeutic agent theophyllin by reduction methods, as set forth in United States Patent No. 569,489 to C. F. Boehringer & Soehne, assignees of Emil Fischer.

This application is a divisional application of this inventors application, Serial No. 142,591, filed February 7, 1903.

A detailed description of the invention by reciting what is considered the best manner of carrying the same into effect will now be given.

Forty-five grams of 8-chlorocaffein are suspended in four hundred cubic centimeters of nitrobenzol, and into this suspension while maintained at atemperature of 50 eentigrade and While constantly stirring or otherwise agitating the same chlorin is introduced in excess. It is preferable to add about 0.5 grams of iodin to the liquor. During the introduction of chlorin solution slowly takes place, and the major portion of the nitrobenzol is then distilled off in a vacuum, the balance of the nitrobenzol being then driven off by means of steam. The residue is then further treated with steam or water in a vaporous or in a gaseous state by passing currents of steam over into the same or otherwise until only a faint odor of formic aldehyde can be noticed. This causes the chlorotheophyllin and a small amount of chlorocaffein to go into solution, while the bulk of the chloroeaifein remains undissolved. The whole is then filtered, and the filtrate is thereupon evaporated to dryness. From the residue the 8-chlorotheophyllin is isolated by extracting with an aqueous solution of ammonia and then precipitating from the ammonical solution by acids.

Having thus fully described the invention, what is claimed as new, and desired to be secured by Letters Patent, is

1. The process which consists in submitting 8-ehlorocaflein to the action of chlorin contained in nitrobenzol.

2. The process which consists in submitting 8-chloroeafi1ein to the action of chlorin contained in nitrobenzol, and then driving ofl? the nitrobenzol.

3. The process which consists in heating 8- 'chlorocafiein with chlorin contained in nitrobenzol, and .then distilling off the nitrobenzol.

4. The process which consists in heating 8- chlorocafl'ein with nitrobenzol containing chlorin in excess.

5. The process which consists in submitting S-chlorocalfein to the action of chlorin contained in nitrobenzol, driving ofi the nitrobenzol, and causing steam toacton the residue.

6. The process which consists in heating 8- chlorocalfein with nitrobenzol containing chlorin in excess, driving ofi the nitrobenzol, and causing steam to act on the residue.

7. The process which consists in submitting 8-ehlorocafi'ein to the action of chlorin contained in nitrobenzol, driving ofl' the nitrobenzol, causing steam to act on the residue, filtering, and drying the filtrate.

8. The process which consists in heating 6- chlorocafi'ein with nitrobenzol containing chlorin in excess, filtering, and drying the liltrate.

9. The process which consists in submitting 8-chlorocafi'ein to the action of chlorin contained in nitrobenzol, driving off the nitrobenzol, causing steam to act on the residue, filtering, drying the filtrate, and isolating the resultant 8-chlorotheophyllin.

10. The process which consists in heating 8- chloroeafi'ein with nitrobenzol containing chlorin in excess, filtering, drying the filtrate, and isolating the resultant 8 cl1lorotl1eo phyllin.

In testimony whereof I afiix my signature in the presence of two witnesses.

MlTFORl) U. MASSHC, Administrator of the estate of Fritz .rlU/l,

deceased.

Witnesses:

E. O. HILDEBRAND, F. H. Souo'r'r. 

